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Design efficiency in genetic association studies

Authors: Miriam Gjerdevik; Håkon K. Gjessing; Julia Romanowska; Øystein A. Haaland; Astanand Jugessur; Nikolai O. Czajkowski; Rolv T. Lie;

Design efficiency in genetic association studies

Abstract

Selecting the best design for genetic association studies requires careful deliberation; different study designs can be used to scan for different genetic effects, and each design has its own set of strengths and limitations. A variety of family and unrelated control configurations are amenable to genetic association analyses, including the case‐control design, case‐parent triads, and case‐parent triads in combination with unrelated controls or control‐parent triads. Ultimately, the goal is to choose the design that achieves the highest statistical power using the lowest cost. For given parameter values and genotyped individuals, designs can be compared directly by computing the power. However, a more informative and general design comparison can be achieved by studying the relative efficiency, defined as the ratio of variances of two different parameter estimators, corresponding to two separate designs. Using log‐linear modeling, we derive the relative efficiency from the asymptotic variance of the parameter estimators and relate it to the concept of Pitman efficiency. The relative efficiency takes into account the fact that different designs impose different costs relative to the number of genotyped individuals. We show that while optimal efficiency for analyses of regular autosomal effects is achieved using the standard case‐control design, the case‐parent triad design without unrelated controls is efficient when searching for parent‐of‐origin effects. Due to the potential loss of efficiency, maternal genes should generally not be adjusted for in an initial genome‐wide association study scan of offspring genes but instead checked post hoc. The relative efficiency calculations are implemented in our R package Haplin.

Country
Norway
Keywords

Genotype, relative (Pitman) efficiency, 620, Applications of statistics to biology and medical sciences; meta analysis, Research Design, Case-Control Studies, case-parent triad, power and sample size, Humans, parent-of-origin effects, Haplin, Genetic Association Studies, Genome-Wide Association Study

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
Green
hybrid